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. 2018 Jul 20:11:4221-4232.
doi: 10.2147/OTT.S168861. eCollection 2018.

CEP55 promotes the proliferation, migration and invasion of esophageal squamous cell carcinoma via the PI3K/Akt pathway

Yang Jia  1 , Zhaohua Xiao  1 , Xin Gongsun  1 , Zhongwei Xin  1 , Bin Shang  1 , Gang Chen  1 , Zhou Wang  1 , Wenpeng Jiang  1
Affiliations

CEP55 promotes the proliferation, migration and invasion of esophageal squamous cell carcinoma via the PI3K/Akt pathway

Yang Jia et al. Onco Targets Ther. .

Abstract

Background: Centrosomal protein 55 (CEP55) is an important prognostic biomarker that plays an essential role in the proliferation, migration and invasion of multiple tumors. We aimed to investigate the prognostic value of CEP55 in pN0 esophageal squamous cell carcinoma (ESCC) and explore its biological function in ESCC cells.

Methods: We used immunohistochemistry and Western blot analysis to detect the expression of CEP55 in ESCC. Furthermore, both in vitro and in vivo assays were used to determine the effect of CEP55 on malignant behavior in ESCC cells.

Results: As expected, we found that CEP55 was overexpressed in ESCC. Univariate and multivariate analyses demonstrated that patients with CEP55 overexpression had a poor prognosis. Additionally, the abilities of proliferation, migration and invasion of cells, as well as the epithelial-mesenchymal transition markers, were all altered with the changed CEP55 expression levels in ESCC cells. Further study elucidated that CEP55 facilitated ESCC via the PI3K/Akt pathway. Blockade of this pathway markedly attenuated CEP55-mediated proliferation, migration, invasion and epithelial-mesenchymal transition of ESCC cells.

Conclusion: Oncogenic CEP55 correlates with a poor prognosis by regulating tumor cell proliferation, migration and invasion via the PI3K/Akt pathway. It can serve as a promising prognostic biomarker and therapeutic target of pN0 ESCC after Ivor-Lewis esophagectomy.

Keywords: CEP55; PI3K/Akt pathway; esophageal squamous cell carcinoma; invasion; migration; proliferation.

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Conflict of interest statement

Disclosure The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Expression of CEP55 in ESCC and its relationship with OS and PFS. Notes: (A) Immunohistochemical staining of CEP55, (magnification ×400). Scale bars, 20 µm. (a) Strong immunostaining in the cytoplasm of tumor cells; (b) weak staining in noncancerous tissue. (B) Western blot analysis showed that CEP55 was overexpressed in ESCC compared with noncancerous tissue. (a) Quantitative analysis of CEP55 protein in 30 pairs of tissue specimens normalized to GAPDH. (b) The bands of CEP55 and GAPDH in eight representative tissue sample pairs. (C) Kaplan–Meier analysis and log-rank test of CEP55 for (a) OS and (b) PFS of patients in pN0 ESCC. The results are expressed as mean ± SD. ***P<0.001. Abbreviations: ESCC, esophageal squamous cell carcinoma; N, noncancerous tissues; OS, overall survival; PFS, progression-free survival; T, tumor tissues.
Figure 2
Figure 2
Cell selection and lentivirus transfection in ESCC cells. Notes: (A) The expression of CEP55 (a) mRNA and (b) protein in cell lines. (B) The expression of CEP55 protein was determined via Western blot analysis. (a) Bands and (b) quantitative analysis of CEP55 and GAPDH in CEP55-deficient Eca109 and KYSE450 cells. (a) Bands and (c) quantitative analysis of CEP55 and GAPDH in CEP55-overexpressed EC9706 cells. The results are expressed as mean ± SD. *P<0.05, **P<0.01, ***P<0.001. Abbreviation: ESCC, esophageal squamous cell carcinoma.
Figure 3
Figure 3
CEP55 promotes the proliferation of ESCC cells. Notes: (A) The viability of (a and b) CEP55-knockdown or (c) CEP55-overexpressed cells was measured with CCK-8 method. (B) Clonogenic assays were applied to evaluate the effect of CEP55 on cell growth. The images of (a and c) colony formation and (b and d) the colony formation rates are exhibited. (C) The tumorigenesis ability of CEP55 in vivo was measured with xenografted tumor models. The (a and c) volume and (b and d) weight of tumors were markedly changed with (a and b) CEP55 depletion or (c and d) overexpression. The results are expressed as mean ± SD. *P<0.05, **P<0.01, ***P<0.001. Abbreviation: ESCC, esophageal squamous cell carcinoma.
Figure 4
Figure 4
CEP55 promotes the migration and invasion of ESCC cells. Notes: (A) The (a and c, magnification ×200) representative images and (b and d, magnification ×200) percentages of cell migration. (B) The (a and c) representative images and (b and d) percentages of cell invasion. (C) Western blotting demonstrated that the expression of EMT-related markers (E-cadherin, N-cadherin, Claudin-1, Vimentin and Snail) was altered with the dysregulated CEP55. The scale bars in A and B are 50 µm. The results are expressed as mean ± SD. **P<0.01, ***P<0.001. Abbreviation: ESCC, esophageal squamous cell carcinoma.
Figure 5
Figure 5
PI3K/Akt pathway is involved in CEP55-mediated cell proliferation, migration, invasion and EMT. Notes: (A) The expression levels of pAktS473 and pAktT308 were altered with the dysregulated CEP55. (B) Blockade of the PI3K/Akt pathway by LY294002, wortmannin and MK2206, respectively, markedly decreased the proliferation, migration, invasion and EMT of ESCC cells. In CEP55-overexpressed EC9706 cells, (a) increased value of OD 450 nm, and enhanced (b) cell migration and (c) invasion were abrogated. (d) The cadherin switching was also reversed. The results are expressed as the mean ± SD. *P<0.05, ***P<0.001. Abbreviations: EMT, epithelial–mesenchymal transition; ESCC, esophageal squamous cell carcinoma.
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